cell-free DNA (cfDNA) Testing vs. Traditional Screening Tests

To the Point– For some conditions, especially Down syndrome, cfDNA has a higher detection rate and a lower false positive rate than traditional screening tests (e.g. quad screen, first trimester screen, etc.). Depending on what particular cfDNA test your doctor orders, cfDNA may also screen for more chromosome abnormalities than traditional screening tests. However, there are things that traditional screening tests can detect that may be missed by cfDNA; pregnancy complications and neural tube defects are just two examples. There are pros and cons to both types of testing; read on for more detailed information.

Some studies indicate that cfDNA has a higher sensitivity and specificity than more traditional screening tests for some of the conditions it screens for, especially for Down syndrome. For example, the quad screen has a sensitivity for Down syndrome of approximately 80% versus 90% or greater for cfDNA. However, recent studies that include the no-call rate are calling into question whether or not the sensitivity and specificity are truly that much higher than traditional screening such as integrated screening. Ultimately, the thought was that the increased sensitivity and specificity of cfDNA may reduce the number of women who screen positive and potentially undergo follow-up invasive testing, such as, amniocentesis; amniocentesis and CVS are associated with risk of miscarriage. Therefore, theoretically, fewer pregnancies would undergo unnecessary risk from invasive procedures. However, given the no-call rates and the growing list of rare conditions that cfDNA screens , we can expect the false positive rate and number of invasive procedures following cfDNA to rise.

cfDNA can be done earlier in pregnancy than some of the traditional screening tests, beginning at 10 weeks gestation and anytime thereafter.

cfDNA screens more chromosome abnormalities than traditional screening tests, such as, sex chromosome abnormalities (X & Y chromosome variations). Some labs also offer screening for other genetic conditions, such as microdeletion syndromes. Ask your provider for more details on what their lab offers. Depending on your needs, beliefs, values and personality, adding more conditions may or may not be better.

Some information available on the internet regarding cfDNA may lead one to believe that this test is provides “yes or no” answers, which is not the case. Although for some conditions it mayhave a much higher sensitivity and specificity than more traditional screening tests, it does not currently equal the accuracy of amniocentesis or CVS. If cfDNA testing is abnormal, there is definitely an increased chance that the baby is indeed affected or has the chromosome condition, but results need to be interpreted with caution. Current guidelines recommend that any abnormal cfDNA be followed up with a diagnostic test, such as CVS or amniocentesis, to confirm these findings. There have been numerous cases where cfDNA came back positve/high-risk and the baby did not have the condition. Likewise, there have been several cases of negative/low-risk cfDNA result and the baby did have one of the conditions that cfDNA screens for.

cfDNA looks for some of the same genetic conditions as traditional screening tests, however, not all. Most of the traditional screening tests look for evidence of open neural tube defects, like spina bifida, and cfDNA does not. However, this can be screened for by ultrasound and a separate blood draw in the second trimester. First and second trimester ultrasounds and other traditional screening tests also have the potential to detect other birth defects and potential pregnancy complications that may be missed by cfDNA.

Currently, cfDNA is not regulated by the FDA. Furthermore, much of the information available regarding how reliable this test is comes from studies funded by the commercial labs and/or authored by individuals associated with one of the commercial labs.